ArticleNature communications2025
A concise enzyme cascade enables the manufacture of natural and halogenated protoberberine alkaloids.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Sustainable Biocatalytic Cascades: A Versatile Tool in the Synthesis of Natural Products With Therapeutic Potential.Chembiochem : a European journal of chemical biology · 2026Review
- Synthesis of the Natural Product Berberine.ACS omega · 2026Article
- Article
- Transaminase and Norcoclaurine Synthase One-Pot Cascades Towards (1S)-Tetrahydroisoquinolines.Chembiochem : a European journal of chemical biology · 2026Article
- Self-Assembled Berberine-Sinapic Acid Nanomedicine for Synergistic Chemotherapy.Molecules (Basel, Switzerland) · 2026Article
- Nature-Inspired Enzymatic Cascades: Emerging Strategies for Sustainable Chemistry.Molecules (Basel, Switzerland) · 2026Review
- Identification and functional verification of key genes involved in alkaloid biosynthesis inFrontiers in plant science · 2026Article
- A Modular Chemoenzymatic Cascade Simplifies Divergent Synthesis of Natural and Unnatural Benzylisoquinoline Alkaloids.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Protein design drives synthetic biology research of plant natural products.Biodesign research · 2025Review
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Authors and funding
7 authors.
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Abstract
The application and drug development of plant-derived natural products are often limited by their low abundance in medicinal plants and the lack of structural complexity and diversity. Herein, we design a concise enzyme cascade to efficiently produce natural and unnatural protoberberine alkaloids from cost-effective, readily available substrates. Through enzyme discovery and engineering, along with systematic optimization of the berberine bridge enzyme to address remaining manufacturing challenges in protoberberine alkaloid biosynthesis, the high production of drug Rotundine is achieved at an impressive gram-scale titer, demonstrating its industrial potential. More importantly, this cascade also enables the efficient biosynthesis of various unnatural halogenated protoberberine alkaloids. Thus, this work not only unlocks the potential of enzyme cascades in overcoming longstanding challenges in the efficient biosynthesis of plant-derived alkaloids, but also opens avenues to introduce structural complexity and diversity into alkaloids through synthetic biology, offering significant potential for drug development.
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Registered trials
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